Cis-dichlorodiammine Pt (II) (cDDP) is an antineoplastic agent which is effective against otherwise resistant solid tumors. It is, however, nephrotoxic and this restricts the dosage and use of this agent. Previous studies in our laboratory have shown that the renal failure induced by cDDP is polyuric in nature and proceeds in distinct time periods from initiation through maintenance and recovery phases. Perhaps related to its renal toxicity is the high renal content of cDDP as compared to other organs. By measuring pressures and flows in vessels and tubules of individual nephrons, the determinants of the fall in glomerular filtration will be determined. Micropuncture of sites along superficial and deep nephrons will be performed to determine the cause of the polyuria. By the use of a radioactive analogue of cDDP, (14C) cisdichloroethylenediammine Pt (II) cDEP, its transport and binding within the kidney will be determined using clearance, and autoradiographic techniques. This information will be used to design new approaches to ameliorate or abort the renal failure and thus increase its anti-neoplastic potential. Understanding the pathophysiology of this model of nephrotoxicity may help in the understanding of other forms of nephrotoxicity.